title: Transcutaneous assessment of renal function in conscious rats with a device for measuring FITC-sinistrin disappearance curves.
abstract: Determination of the urinary or plasma clearance of exogenous renal markers, such as inulin or iohexol, is considered to be the gold standard for glomerular filtration rate (GFR) measurement. Here, we describe a technique allowing determination of renal function based on transcutaneously measured elimination kinetics of fluorescein isothiocyanate (FITC)-sinistrin, the FITC-labeled active pharmaceutical ingredient of a commercially available marker of GFR. A low cost device transcutaneously excites FITC-sinistrin at 480  nm and detects the emitted light through the skin at 520  nm. A radio-frequency transmission allows remote monitoring and real-time analysis of FITC-sinistrin excretion as a marker of renal function. Due to miniaturization, the whole device fits on the back of freely moving rats, and requires neither blood sampling nor laboratory assays. As proof of principle, comparative measurements of transcutaneous and plasma elimination kinetics of FITC-sinistrin were compared in freely moving healthy rats, rats showing reduced kidney function due to unilateral nephrectomy and PKD/Mhm rats with cystic kidney disease. Results show highly comparable elimination half-lives and GFR values in all animal groups. Bland-Altman analysis of enzymatically compared with transcutaneously measured GFR found a mean difference (bias) of 0.01 and a -0.30 to 0.33 ml/min per 100 g body weight with 95% limit of agreement. Thus, with this device, renal function can be reliably measured in freely moving rats eliminating the need for and influence of anesthesia on renal function.
authors.affiliation: Medical Research Centre, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Schock-Kusch
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
authors.forename: Yury
authors.initials: Y
authors.lastname: Shulhevich
authors.forename: Juergen
authors.initials: J
authors.lastname: Hesser
authors.forename: Dzmitry
authors.initials: D
authors.lastname: Stsepankou
authors.forename: Maliha
authors.initials: M
authors.lastname: Sadick
authors.forename: Stefan
authors.initials: S
authors.lastname: Koenig
authors.forename: Friederike
authors.initials: F
authors.lastname: Hoecklin
authors.forename: Johannes
authors.initials: J
authors.lastname: Pill
authors.forename: Norbert
authors.initials: N
authors.lastname: Gretz
mesh_terms: D000818:Animals; D003243:Consciousness; D004195:Disease Models, Animal; D004867:Equipment Design; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology* / Q000601:surgery; D008904:Miniaturization; D008954:Models, Biological; D018670:Monitoring, Ambulatory / Q000295:instrumentation / Q000379:methods*; D009392:Nephrectomy; D009844:Oligosaccharides / Q000493:pharmacokinetics; D007690:Polycystic Kidney Diseases / Q000175:diagnosis* / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats
chemical_list: D005456:Fluorescent Dyes; D009844:Oligosaccharides; D016650:Fluorescein-5-isothiocyanate; C064636:sinistrin